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Diabetes is associated with disturbances of brain activity and cognitive impairment. We hypothesize that ceramides may constitute an important contribution to diabetes-linked neuro-dysfunction. In our study we used rats injected with streptozotocin (STZ) as a model of severe hyperglycemia. Using the gas-liquid chromatography technique we found a significant increase of ceramide content in brains and a decrease in plasma of diabetic rats. The inhibitor of serine palmitoyltransferase, myriocin, reduced ceramide generation in hyperglycemic brains, although injected alone it exerted a paradoxical effect of ceramide upregulation. Myriocin had no impact on ceramide concentration in the plasma of either control or diabetic rats. The level of ceramide saturated fatty acids was elevated whereas the level of ceramide poly-unsaturated fatty acids was downregulated in brains of all experimental groups. The concentration of ceramide mono-unsaturated fatty acids remained unchanged. The pattern of individual ceramide species was altered depending on treatment. We noted an STZ-evoked increase of brain ceramide C16:0, C18:0 and C20:0 and a strong decline in ceramide C18:2 fatty acid levels. Some changes of brain ceramide pattern were modified by myriocin. We found a decreased amount of total ceramide-ω-6 fatty acids in STZ-treated rat brains and no changes in ceramide-ω-3 concentration. We conclude that ceramides may be important mediators of diabetes-accompanied brain dysfunction., (© 2012 The Authors Journal compilation © 2012 FEBS.)

Aims/hypothesis: Ceramide is the main second messenger in the sphingomyelin-transmembrane signalling pathway. The compound is likely to play a role in the induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin diabetes on the content and composition of ceramides and sphingomyelins and the activity of neutral Mg (2+)-dependent sphingomyelinase and acid sphingomyelinase in different types of skeletal muscle of the rat., Methods: The experiments were carried out on two groups of male Wistar rats weighing 250-280 g: controls and those treated with streptozotocin at a dose of 60 mg/kg. Determinations were performed on three types of skeletal muscle: the slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic (red section of the gastrocnemius) and fast-twitch glycolytic (white section of the same muscle). The content and composition of ceramide- and sphingomyelin-fatty acids were determined using gas-liquid chromatography. The activity of the enzymes was measured using N-[(14)CH (3)]-sphingomyelin as the substrate., Results: Twelve different ceramides and sphingomyelins were identified and quantified in each muscle with regard to the fatty acid residue. The ratio of total content of ceramide-saturated fatty acids to the total content of ceramide-unsaturated fatty acids was more than two. In the case of sphingomyelin, the ratio was similar to ceramide in the soleus and much higher in both sections of the gastrocnemius. Treatment with streptozotocin increased the total content of ceramide-fatty acids by 78% (p < 0.001) in the soleus, 27.5% (p < 0.01) in the red and 36.9% (p < 0.001) in the white section of the gastrocnemius. Concomitantly, the total content of sphingomyelin-fatty acids decreased by 43.8%, 31.2%, 24.8% (p < 0.001 in each case) in the respective muscles. The activity of neutral Mg (2+)-dependent sphingomyelinase was elevated by 69.5%, 105.9% and 62.3% in the soleus and red and white gastrocnemius, respectively (p < 0.001 for each muscle). The activity of acid sphingomyelinase was stable in the soleus and white gastrocnemius and decreased by 15.7% (p < 0.01) in the red gastrocnemius., Conclusion/interpretation: The results obtained show that insulin deficiency results in elevation in the content of ceramide in skeletal muscles. This indicates that the hormone is involved in regulation of the activity of the sphingomyelin-signalling pathway in the muscles.

The aim of the present study was to examine the effect of acute streptozotocin diabetes on the content of different phospholipids and the incorporation of blood-borne 14C-palmitic acid into the phospholipid moieties in the rat liver nuclei. Diabetes was produced by intravenous administration of streptozotocin, and determinations were carried out two and seven days thereafter. Phospholipids were extracted from isolated nuclei and separated into the following fractions: sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine and cardiolipin. Following that, they were quantified and radioactivity was measured. It was found that, in comparison to non-diabetic controls, two-day diabetes reduced the total content of phospholipids in the nuclei by 9.6%. The content of phospholipids in the nuclei by 9.6%. The content of phosphatidylcholine and phosphatidylserine was reduced and the content of the remaining phospholipids was stable. The specific activity of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and cardiolipin, based on radioactivity incorporated from 14C-palmitic acid, was elevated. Seven-day diabetes resulted in a reduction of the total phospholipid content in the nuclei by 39.4%. This was accounted for by a reduction in the content of each phospholipid fraction with the exception of cardiolipin. The specific activity of each phospholipid fraction, was elevated in this group. It is concluded that insulin is involved in the regulation of the nuclear phospholipid content.

The aim of the present study was to examine the effect of acute streptozotocin diabetes on long chain fatty acid content and composition in different lipid classes of particular muscle types in the rat. Two days after streptozotocin administration, rats were anesthetised, and the white and red sections of the gastrocnemius, the soleus and the blood were taken. Lipids were extracted with chloroform/methanol and separated into different fractions (phospholipids, free fatty acids, di- and triacylglycerols) by means of thin layer chromatography. Fatty acids of each fraction were identified and quantified by means of gas-liquid chromatography. The diabetes resulted in elevation of the concentration of blood glucose (over four-fold) and the plasma free fatty acid (over two-fold). Total free fatty acid content in the muscles of diabetic rats increased by 26% in the white, 24% in the red gastrocnemius and 21% in the soleus. There were also changes in the composition of that fraction in each muscle. Diacylglycerol fatty acid content was elevated in both parts of the gastrocnemius (the white part by 15%, the red part by 44%) and remained stable in the soleus of the diabetic rats. The content of triacylglycerol fatty acids was elevated only in the red gastrocnemius in the diabetic group (by 112%), but changes in fatty acid composition in this fraction occurred in each muscle. The content of phospholipid fatty acids was elevated in the white gastrocnemius (by 13%) and remained stable in other muscles. There were only minor changes in phospholipid fatty acid composition in the diabetic rats. We concluded that acute insulin deficiency changes fatty acid content and composition in skeletal muscle lipids. The changes depend both on lipid fraction and muscle type.